Boxed warningThe FDA label of this medicine carries a boxed warning, the strongest warning the FDA gives. Read it under warnings and precautions.
Indications
XOLAIR is an anti-IgE antibody indicated for: Moderate to severe persistent asthma in adults and pediatric patients 6 years of age and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids ( 1.1 ) Chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients 18 years of age and older with inadequate response to nasal corticosteroids, as add-on maintenance treatment ( 1.2 ) IgE-mediated food allergy in adult and pediatric patients aged 1 year and older for the reduction of allergic reactions (Type I), including anaphylaxis, that may occur with accidental exposure to one or more foods.
To be used in conjunction with food allergen avoidance ( 1.3 ) Chronic spontaneous urticaria (CSU) in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine treatment ( 1.4 ) Limitations of Use : Not indicated for acute bronchospasm or status asthmaticus. ( 1.1 , 5.3 ) Not indicated for the emergency treatment of allergic reactions, including anaphylaxis ( 1.3 ) Not indicated for other forms of urticaria.
( 1.4 )
1.1Asthma
XOLAIR is indicated for adults and pediatric patients 6 years of age and older with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids. Limitations of Use: XOLAIR is not indicated for the relief of acute bronchospasm or status asthmaticus.
1.2Chronic Rhinosinusitis with Nasal Polyps
XOLAIR is indicated for add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients 18 years of age and older with inadequate response to nasal corticosteroids.
1.3IgE-Mediated Food Allergy
XOLAIR is indicated for the reduction of allergic reactions (Type I), including anaphylaxis, that may occur with accidental exposure to one or more foods in adult and pediatric patients aged 1 year and older with IgE-mediated food allergy. XOLAIR is to be used in conjunction with food allergen avoidance. Limitations of Use: XOLAIR is not indicated for the emergency treatment of allergic reactions, including anaphylaxis.
XOLAIR is indicated for the treatment of adults and adolescents 12 years of age and older with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment. Limitations of Use: XOLAIR is not indicated for treatment of other forms of urticaria.
Contraindications
XOLAIR is contraindicated in patients with severe hypersensitivity reaction to XOLAIR or any ingredient of XOLAIR [see Warnings and Precautions (5.1) ] . Severe hypersensitivity reaction to XOLAIR or any ingredient of XOLAIR ( 4 , 5.1 )
Warnings and precautions
Anaphylaxis: Initiate XOLAIR therapy in a healthcare setting prepared to manage anaphylaxis which can be life-threatening and observe patients for an appropriate period of time after administration. ( 5.1 ) Malignancy: Malignancies have been observed in clinical studies. ( 5.2 ) Acute Asthma Symptoms: Do not use for the treatment of acute bronchospasm or status asthmaticus. ( 5.3 ) Corticosteroid Reduction: Do not abruptly discontinue corticosteroids upon initiation of XOLAIR therapy.
( 5.4 ) Eosinophilic Conditions: Be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy, especially upon reduction of oral corticosteroids. ( 5.5 ) Fever, Arthralgia, and Rash: Stop XOLAIR if patients develop signs and symptoms similar to serum sickness. ( 5.6 ) Potential Medication Error Related to Emergency Treatment of Anaphylaxis: XOLAIR should not be used for emergency treatment of allergic reactions, including anaphylaxis.
( 5.9 )
5.1Anaphylaxis
Anaphylaxis has been reported to occur after administration of XOLAIR in premarketing clinical trials and in postmarketing spontaneous reports [see Boxed Warning and Adverse Reactions (6.2) ] . Signs and symptoms in these reported cases have included bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue. Some of these events have been life-threatening. In premarketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3507 (0.1%) patients.
Anaphylaxis occurred with the first dose of XOLAIR in two patients and with the fourth dose in one patient. The time to onset of anaphylaxis was 90 minutes after administration in two patients and 2 hours after administration in one patient. A case-control study in asthma patients showed that, among XOLAIR users, patients with a history of anaphylaxis to foods, medications, or other causes were at increased risk of anaphylaxis associated with XOLAIR, compared to those with no prior history of anaphylaxis [see Adverse Reactions (6.1) ] .
In postmarketing spontaneous reports, the frequency of anaphylaxis attributed to XOLAIR use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. Anaphylaxis has occurred as early as after the first dose of XOLAIR, but also has occurred beyond one year after beginning regularly scheduled treatment. Approximately 60% to 70% of anaphylaxis cases have been reported to occur within the first three doses of XOLAIR, with additional cases occurring sporadically beyond the third dose.
Initiate XOLAIR only in a healthcare setting equipped to manage anaphylaxis, which can be life-threatening. Observe patients closely for an appropriate period of time after administration of XOLAIR, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials and postmarketing spontaneous reports [see Adverse Reactions (6.1 , 6.2) ] . Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs or symptoms occur.
Once XOLAIR therapy has been established, administration of XOLAIR prefilled syringe or autoinjector outside of a healthcare setting by a patient or a caregiver may be appropriate for selected patients. Patient selection, determined by the healthcare provider in consultation with the patient, should take into account the pattern of anaphylaxis events seen in premarketing clinical trials and postmarketing spontaneous reports, as well as individual patient risk factors (e.g., prior history of anaphylaxis), ability to recognize signs and symptoms of anaphylaxis, and ability to perform subcutaneous injections with XOLAIR prefilled syringe or autoinjector with proper technique according to the prescribed dosing regimen and Instructions for Use [see Dosage and Administration (2.6) , Adverse Reactions (6.1 , 6.2) ].
Discontinue XOLAIR in patients who experience a severe hypersensitivity reaction [see Contraindications (4) ] .
5.2Malignancy
Malignant neoplasms were observed in 20 of 4127 (0.5%) XOLAIR-treated patients compared with 5 of 2236 (0.2%) control patients in clinical studies of adults and adolescents ≥12 years of age with asthma and other allergic disorders. The observed malignancies in XOLAIR-treated patients were a variety of types, with breast, non-melanoma skin, prostate, melanoma, and parotid occurring more than once, and five other types occurring once each.
The majority of patients were observed for less than 1 year. The impact of longer exposure to XOLAIR or use in patients at higher risk for malignancy (e.g., elderly, current smokers) is not known. In a subsequent observational study of 5007 XOLAIR-treated and 2829 non-XOLAIR-treated adolescent and adult patients with moderate to severe persistent asthma and a positive skin test reaction or in vitro reactivity to a perennial aeroallergen, patients were followed for up to 5 years.
In this study, the incidence rates of primary malignancies (per 1000 patient years) were similar among XOLAIR-treated (12.3) and non-XOLAIR-treated patients (13.0) [see Adverse Reactions (6.1) ] . However, study limitations preclude definitively ruling out a malignancy risk with XOLAIR. Study limitations include: the observational study design, the bias introduced by allowing enrollment of patients previously exposed to XOLAIR (88%), enrollment of patients (56%) while a history of cancer or a premalignant condition were study exclusion criteria, and the high study discontinuation rate (44%).
5.3Acute Asthma Symptoms and Deteriorating Disease
XOLAIR has not been shown to alleviate asthma exacerbations acutely. Do not use XOLAIR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with XOLAIR.
5.4Corticosteroid Reduction Do
not discontinue systemic or inhaled corticosteroids abruptly upon initiation of XOLAIR therapy for asthma or CRSwNP. Decrease corticosteroids gradually under the direct supervision of a physician. In CSU patients, the use of XOLAIR in combination with corticosteroids has not been evaluated.
5.5Eosinophilic Conditions
In rare cases, patients with asthma on therapy with XOLAIR may present with serious systemic eosinophilia sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients.
A causal association between XOLAIR and these underlying conditions has not been established.
5.6Fever, Arthralgia, and Rash
In post-approval use, some patients have experienced a constellation of signs and symptoms including arthritis/arthralgia, rash, fever, and lymphadenopathy with an onset 1 to 5 days after the first or subsequent injections of XOLAIR. These signs and symptoms have recurred after additional doses in some patients. Although circulating immune complexes or a skin biopsy consistent with a Type III reaction were not seen with these cases, these signs and symptoms are similar to those seen in patients with serum sickness.
Physicians should stop XOLAIR if a patient develops this constellation of signs and symptoms [see Adverse Reactions (6.2) ] .
5.7Parasitic (Helminth) Infection
Monitor patients at high risk of geohelminth infection while on XOLAIR therapy. Insufficient data are available to determine the length of monitoring required for geohelminth infections after stopping XOLAIR treatment. In a one-year clinical trial conducted in Brazil in adult and adolescent patients at high risk for geohelminthic infections (roundw
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
No formal drug interaction studies have been performed with XOLAIR. In patients with asthma, CRSwNP, and IgE-mediated food allergy the concomitant use of XOLAIR and allergen immunotherapy has not been evaluated . In patients with CSU, the use of XOLAIR in combination with immunosuppressive therapies has not been studied. No formal drug interaction studies have been performed. ( 7 )
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
A registry study of XOLAIR exposure during pregnancy showed no increase in the rate of major birth defects or miscarriage. There was an increased rate of low birth weight among registry infants compared to infants in the other cohorts, despite average gestational age at birth; however, women taking XOLAIR during pregnancy also had more severe asthma, which makes it difficult to determine whether the low birth weight is due to the drug or the disease severity [see Data ] .
There are risks associated with poorly or moderately controlled asthma in pregnancy [see Clinical Considerations ] . Human IgG antibodies are known to cross the placental barrier; therefore, XOLAIR may be transmitted from the mother to the developing fetus. In animal reproduction studies, no evidence of fetal harm was observed in Cynomolgus monkeys with subcutaneous doses of omalizumab up to approximately 5 times the maximum recommended human dose (MRHD) [see Data ] .
The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.
The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control. Data Human Data A prospective cohort pregnancy exposure registry study conducted in the US from 2006 to 2018, included 250 pregnant women with asthma treated with XOLAIR. Of these, 246 patients were exposed to XOLAIR in the first trimester of pregnancy, and the median exposure duration was 8.7 months.
The registry findings for applicable mother and infant subgroups were compared to age-adjusted frequencies in a disease-matched external cohort of 1,153 pregnant women with asthma (without exposure to XOLAIR) identified from healthcare databases of residents in the Canadian province of Quebec, and referred to as the Quebec External Comparator Cohort ("comparator cohort"). Among applicable registry infants, the prevalence of major congenital anomalies (8.1%) was similar to that for infants in the comparator cohort (8.9%).
Among applicable registry pregnancies, 99.1% led to live births, similar to 99.3% for the comparator cohort. There was an increased rate of low birth weight among registry infants (13.7%) as compared to the comparator cohort (9.8%); however, women taking XOLAIR during pregnancy also had more severe asthma, which makes it difficult to determine whether the low birth weight is due to the drug or the disease severity. The registry study cannot definitively establish the absence of any risk because of methodological limitations, including the observational nature of the registry, small sample size, and potential differences between the registry population and the comparator cohort.
Animal Data Reproductive studies have been performed in Cynomolgus monkeys. There was no evidence of maternal toxicity, embryotoxicity, or teratogenicity when omalizumab was administered throughout the period of organogenesis at doses that produced exposures approximately 5 times the MRHD (on a mg/kg basis with maternal subcutaneous doses up to 75 mg/kg/week). Omalizumab did not elicit adverse effects on fetal or neonatal growth when administered throughout late gestation, delivery, and nursing.
Adverse reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Anaphylaxis [see Boxed Warning and Warnings and Precautions (5.1) ] Malignancies [see Warnings and Precautions (5.2) ] Asthma : The most common adverse reactions (≥ 1% of patients) in clinical studies with adult and adolescent patients ≥12 years of age were arthralgia, pain (general), leg pain, fatigue, dizziness, fracture, arm pain, pruritus, dermatitis, and earache.
In clinical studies with pediatric patients 6 to <12 years of age, the most common adverse reactions (≥3% of patients) were nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bites, and epistaxis. ( 6.1 ) Chronic Rhinosinusitis with Nasal Polyps : The most common adverse reactions (≥ 3% of patients) in clinical studies with adult patients included the following: headache, injection site reaction, arthralgia, upper abdominal pain, and dizziness.
( 6.1 ) IgE-Mediated Food Allergy : The most common adverse reactions (≥3% of patients) were injection site reactions and pyrexia. ( 6.1 ) Chronic Spontaneous Urticaria : The most common adverse reactions (≥2% of patients) included the following: nausea, nasopharyngitis, sinusitis, upper respiratory tract infection, viral upper respiratory tract infection, arthralgia, headache, and cough. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions from Clinical Studies in Adult and Adolescent Patients 12 Years of Age and Older with Asthma The data described below reflect XOLAIR exposure for 2076 adult and adolescent patients ages 12 and older, including 1687 patients exposed for six months and 555 exposed for one year or more, in either placebo-controlled or other controlled asthma studies.
The mean age of patients receiving XOLAIR was 42 years, with 134 patients 65 years of age or older; 60% were women, and 85% Caucasian. Patients received XOLAIR 150 mg to 375 mg every 2 or 4 weeks or, for patients assigned to control groups, standard therapy with or without a placebo. The adverse reactions most frequently resulting in clinical intervention (e.g., discontinuation of XOLAIR, or the need for concomitant medication to treat an adverse reaction) were injection site reaction (45%), viral infections (23%), upper respiratory tract infection (20%), sinusitis (16%), headache (15%), and pharyngitis (11%).
These reactions were observed at similar rates in XOLAIR-treated patients and control patients. Table 7 shows adverse reactions from four placebo-controlled asthma trials that occurred ≥1% and more frequently in adult and adolescent patients 12 years of age and older receiving XOLAIR than in those receiving placebo. Adverse reactions were classified using preferred terms from the International Medical Nomenclature (IMN) dictionary.
Injection site reactions were recorded separately from the reporting of other adverse reactions. Table 7. Adverse Reactions ≥1% More Frequent in XOLAIR-Treated Adult or Adolescent Patients 12 years of Age and Older in Four Placebo-controlled Asthma Trials Adverse reaction XOLAIR n=738 Placebo n=717 Body as a whole Pain 7% 5% Fatigue 3% 2% Musculoskeletal system Arthralgia 8% 6% Fracture 2% 1% Leg pain 4% 2% Arm pain 2% 1% Nervous system Dizziness 3% 2% Skin and appendages Pruritus 2% 1% Dermatitis 2% 1% Special senses Earache 2% 1% There were no differences in the incidence of adverse reactions based on age (among patients under 65), gender or race.
Anaphylaxis Case Control Study A retrospective case-control study investigated risk factors for anaphylaxis to XOLAIR among patients treated with XOLAIR for asthma. Cases with an adjudicated history of anaphylaxis to XOLAIR were compared to controls with no such history. The study found that a self-reported history of anaphylaxis to foods, medications or other causes was more common among patients with XOLAIR anaphylaxis (57% of 30 cases) compared to controls (23% of 88 controls) [OR 8.1, 95% CI 2.7 to 24.3].
Because this is a case-control study, the study cannot provide the incidence of anaphylaxis among XOLAIR users. From other sources, anaphylaxis to XOLAIR was observed in 0.1% of patients in clinical trials and at least 0.2% of patients based upon postmarketing reports. Approximately 60% to 70% of cases were reported to occur within the first three doses of XOLAIR, with additional cases occurring sporadically beyond the third dose.
The time to onset for anaphylaxis was reported to occur within 2 hours for the majority of cases (approximately 75%) [see Warnings and Precautions (5.1) , Adverse Reactions (6.2) ] . Injection Site Reactions In adults and adolescents, injection site reactions of any severity occurred at a rate of 45% in XOLAIR-treated patients compared with 43% in placebo-treated patients. The types of injection site reactions included: bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation.
Severe injection site reactions occurred more frequently in XOLAIR-treated patients compared with patients in the placebo group (12% versus 9%). The majority of injection site reactions occurred within 1 hour post injection, lasted less than 8 days, and generally decreased in frequency at subsequent dosing visits. Adverse Reactions from Clinical Studies in Pediatric Patients 6 to <12 Years of Age with Asthma The data described below reflect XOLAIR exposure for 926 patients 6 to <12 years of age, including 583 patients exposed for six months and 292 exposed for one year or more, in either placebo-controlled or other controlled asthma studies.
The mean age of pediatric patients receiving XOLAIR was 8.8 years; 69% were male, and 64% were Caucasian. Pediatric patients received XOLAIR 75 mg to 375 mg every 2 or 4 weeks or, for patients assigned to control groups, standard therapy with or without a placebo. No cases of malignancy were reported in patients treated with XOLAIR in these trials. The most common adverse reactions occurring at ≥3% in the pediatric patients receiving XOLAIR and more frequently than in patients treated with placebo were nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bite, and epistaxis.
The adverse reactions most frequently resulting in clinical intervention (e.g., discontinuation of XOLAIR, or the need for concomitant medication to treat an adverse event) were bronchitis (0.2%), headache (0.2%) and urticaria (0.2%). These reactions were observed at similar rates in XOLAIR-treated patients and control patients. Adverse Reactions from Clinical Studies in Adult Patients with Chronic Rhinosinusitis with Nasal Polyps The data described below reflect XOLAIR exposure for 135 patients ≥ 18 years of age, exposed for six months in two placebo-controlled studies.
The mean age of patients receiving XOLAIR was 49.7 years; 64% were male, and 94% were Caucasian. Patients received XOLAIR or placebo SC every 2 or 4 weeks, with dosage and frequency according to Table 3 . All patients received background nasal mometasone therapy throughout the study. Table 8 lists the adverse reactions occurring in ≥3% of XOLAIR-treated patients and more frequently than in patients treated with placebo in chronic rhinosinusitis with nasal polyps (CRSwNP) Trials 1 and 2; results were pooled.
Table 8. Adverse Reactions Occurring in ≥3% of XOLAIR-Treated Patients and More Frequently than in Patients Treated with Placebo in CRSwNP Trials 1 and 2 Adverse reaction XOLAIR n=135
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
OMALIZUMAB 150MG/VIAL
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
